PolG Inhibits Glycolysis by Suppressing PKM2 Phosphorylation Resulting Reduced Gastric Cancer Proliferation

Abstract Background: Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death. There is a critical need for the development of novel therapies in GC. DNA polymerase gamma (PolG) has been implicated in mitochondrial homeostasis and affects the development of a numerous of cancer types. However, its effects in GC and molecular mechanisms remain to be fully determined. Methods: GSE62254 dataset was used to predict the impact of PolG on prognostic valule in GC patients. Lentivirus-mediated transduction was used to silence PolG expression. Western blot analysis the knockdown effect. Co-immunoprecipitation analysis was performed to explore the potential molecular mechanism. Analysis of the glycolysis process in GC cells was also performed. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay. Cell migration was detected using transwell method. Animal experiment was used to measure the In vivo xenograft tumor growth.Results: GC patients with low PolG expression have worse OS and pFS . PolG binds to PKM2 and affects the activation of the Tyr105 site phosphorylation, then interfering with the glycolysis of Gastric cancer cells. In vitro tumor formation experiments in mice also confirmed that PolG knockdown GC has stronger proliferation ability. PolG can suppress GC cells growth in both vivo and vitro.Conclusion: Our study reveals a potential molecular mechanism between PolG and the energy metabolic process of GC tumor cells, suggesting PolG as an independent novel potential therapeutic target for tumor therapy.